As is known, microfluidic devices are being used in an increasing number of applications including various traditional laboratory tasks. These tasks are implemented at the microscale level in order to realize the potential of comprehensive lab-on-a-chip (LOC) components such as pumps, filters, and mixers. These LOC components may be coupled together in various ways to accomplish tasks such as aliquoting specific volumes of liquid into a microchannel or mixing together reagents and observing the result in a detection microchannel. A task that has received only limited attention thus far is sample concentration.
The ability of microfluidic systems to manipulate small volumes of fluid is one of the strengths of such systems. However, since only small volumes of fluid are manipulated, the concentrations of molecules in the fluid are difficult to detect. It can be appreciated that obtaining a sample concentration of molecules in fluid flowing through the microfluidic system is a necessary task in almost any LOC system. Hence, it is highly desirable to provide a method of obtaining a sample concentration that is simple to incorporate into any microfluidic device design regardless of the method implemented for pumping fluid through a channel of a microfluidic device, the material from which the microfluidic device is constructed, or the nature of the sample (i.e., organic or inorganic) to be concentrated.
By way of example, the most common application wherein a sample concentration must be obtained is capillary electrophoresis (CE). The three most popular methods for obtaining the sample concentration in CE are: field-amplified sample stacking; isotachophoresis; and solid-phase extraction. Field-amplified sample stacking is performed by electrokinetically pulling a sample of fluid from a region of low buffer concentration into a region of high buffer concentration. The difference in buffer concentration affects the sample velocity by slowing or “stacking,” the sample within the high concentration buffer adjacent the interface. Isotachophoresis involves the use of electrolytes of different mobility. The sample of fluid is positioned between so-called leading and trailing electrolytes. The sample separates into zones of different mobility wherein each zone has a concentration proportional to the leading electrolyte concentration. Solid-phase extraction involves the treatment of a surface or the packing of the microchannels of the microfluidic device with treated solids in order to attract the molecule of interest. A solution containing the molecules to be concentrated is flowed over the treated surface such that the molecules concentrate at the treated surface.
It can be understood that these prior methods require that the sample of fluid have an appropriate charge or that the molecules of the sampled fluid have the ability to be bound to a specific molecule. An alternate technique that is free from the constraints of prior methods is ultrasonic acoustic particle trapping. However, ultrasonic acoustic particle trapping requires complex microfabrication processing and can be difficult to integrate into microfluidic device designs. It can be appreciated that the ideal method of obtaining a sample concentration should incorporate all the benefits of the previous methods, heretofore described, without the drawbacks.
Therefore, it is a primary object and feature of the present invention to provide a method of obtaining a sample concentration of particles from a solution in a microfluidic device that is simple and inexpensive to implement.
It is a further object and feature of the present invention to provide a method of obtaining a sample concentration of particles from a solution in a microfluidic device that may be utilized with microfluidic devices of any design regardless of the method implemented for pumping fluid through a channel of the microfluidic device, the material from which the microfluidic device is constructed, or the nature of the particles (i.e., organic or inorganic) to be sampled.
It is a still object and feature of the present invention to provide a method of obtaining a sample concentration of particles from a solution in a microfluidic device that does not damage the particles or molecules in the solution to be sampled.
In accordance with the present invention, a method is provided of obtaining a sample concentration of particles from a solution in a microfluidic device. The microfluidic device includes a channel having a reservoir port and a collection port. The reservoir port can be any type of liquid/gas interface. The method includes the step of filling the channel with the solution, the solution having particles therein. A reservoir drop is deposited on the reservoir port of sufficient volume to supply the channel with fluid. The solution at the collection port of the channel is allowed to evaporate such that the particles concentrate at the collection port.
The reservoir drop may be formed from the solution or from another fluid. A portion of the solution adjacent the collection port is removed to obtain the sample concentration. A boundary condition may be introduced adjacent to the collection port to control the evaporation of the solution. The boundary condition may include passing a stream of air over the collection port to facilitate evaporation of the solution or positioning a sorption agent adjacent the collection port to facilitate evaporation of the solution. A second reservoir drop may be deposited at the reservoir port of the channel as the first reservoir drop flows into the channel.
In accordance with a further aspect of the present invention, a method is provided of obtaining a sample concentration. The method includes the step of providing a microfluidic device having a channel therethrough. The channel includes a reservoir port and a collection port. The channel is filled with a fluid having particles therein. A portion of the fluid at the collection port is evaporated so as to generate a pressure gradient between the fluid at the reservoir port and the fluid at the collection port such that the fluid flows through the channel towards the collection port and such that the particles in fluid concentrate at the collection port.
A reservoir drop of a reservoir solution is deposited over the reservoir part of the channel of sufficient dimension to overlap the reservoir port of the channel. It is contemplated that the reservoir solution be the fluid. A second reservoir drop may be deposited at the reservoir port of the channel as the first reservoir drop flows into the channel.
A second portion of the fluid adjacent the collection port may be drawn to obtain the sample concentration. A stream of air may be passed over the collection port to facilitate evaporation of the fluid. Alternatively, a sorption agent may be positioned adjacent the collection port to facilitate evaporation of the fluid.
In accordance with a further aspect of the present invention, a method is provided of obtaining a sample concentration of particles from a solution in a microfluidic device. The microfluidic device includes a channel having a reservoir port of a predetermined radius and a collection port of a predetermined radius. The method includes the step of filling the channel with the solution having particles therein. A reservoir drop is deposited over the reservoir part of the channel such that the solution of the channel flows towards the collection port in response to evaporation of the solution at the collection port. Thereafter, the particles at the collection port may be collected.
The reservoir drop may be formed from the solution or an alternate fluid. The step of collecting the particles includes the additional step of removing a portion of the solution adjacent the collection port to obtain the sample concentration. In order to facilitate evaporation of the solution, a stream of air may be passed over the collection port. Alternatively, a sorption agent may be positioned adjacent to the collection port to facilitate evaporation of the solution. A second reservoir drop may be deposited at the reservoir port of the channel as the first reservoir drop flows into the channel.